Manufacture of thiocarbazides of the naphthalene series



Patented June 12, 1928.

PAT

FFICE.

GEORGE MALCOLM DYSON, OF MANCHESTER, FREDERICK ALFRED MASON, OF BLACK- LEY, MANCHESTER, AND ARNOLD RENSHAW, F"MANCHESTER, ENGLAND, AS. SIGN ORS TO BRITISH DYESTUFES CORPORATION LIMITED, 0}? MANCHESTER, ENG- LAND, A CORPORATION OF GREAT BRITAIN DIRELAND.

MANUFACTURE OF THIOOARIBAZIDES OF THE NAPHTHALENE SERIES.

No Drawing. Application filed May-12, 1927, Serial No. 190,958, and inGreat Britain May 25, 1926.

In the specification of British Letters Patent Nos. 9,472 and 2,192 of 191&, the manufacture of ureas and thioureas of the naphthalene series is described; and again in the specification of British Letters Patent No. 224,849, the manufacture of one particular symmetrical urea is described, and this specificaton refers to a number of British and other patents relating to the manufacture of allied substances. All the patents referred to deal with the production of ureas or thioureas, and nothing is said with reference to the production 'of thiocarbazides from similar materials, let alone as to the 1 properties possessed by such bodies.-

We have found that new thiocarbazides can be obtained as hereinafter set forth which are of value as therapeutic agents for the destruction of blood parasites, although comparatively non-toxic to man and higher animals, and as intermediates for the manufacture'of colouring matters.

WVe have found that by the action of aromatic carboxylic or sulphonic halides which contain in the aromatic nucleus a nitro group upon sulphonated amines or aminophenols of the naphthalene or acenaphthene series, or upon derivatives of these, containing always an .NH. group in the oc-POSltlOll, N- 0 acidyl substituted compounds'are obtained, which, after reduction of the nitro group followed. by diazotization of the new amino group and reduction of the diazo compound so formed, yield hydrazines, which by treat- 11161113 with thiophosgene (GSCIQ are converted intothe corresponding thiocarbazides. Further we have found that, after reduction of thenitro group as aforesaid, the result ing amino compound, instead of being dia- 40 zotized and reduced, may be treated with the same nitro-arom'atic acidyl halide as initial- 1y used or with a different nitro-aromatic acidyl halide, and the new nitro group may be reduced to give the correspondingamino derivative. By repeating these operations, the amino-acidyl residue can be successively introduced two or more times into the mole-' cule. From these compounds the corresponding thiocarbazides can be produced, as

chlorides,

above described, by diazotization, reduction 5 and treatment with thiophosgene.

As'examples of substituents for the pro duction, of the substitued naphthyl a minesulphonic acids may be mentioned 2-nitrocifi namyl chloride (Berichte 16, 34, Beilstein 2, 14:14, 3rd edition), 3-nitrocinnamyl chloride (German Patents 288,272 and 288,273), 4- nitrocinnamyl chloride (Berichte 1916, 49, 2688) l-nit'ro-naphthalene 5 sulpho chloride, lz5-nitronaphthoyl chloride, 2-nitrophneylacetyl chloride (Berichte 43, 2547), L-nitrophenylacetyl chloride, nitrobenzoy'l chlorides, nitroanisoyl chlorides, nitrotoluyl nitrobenzene sulphochlorides, chloro-nitrobenzoyl chlorides, bromonitrobenzoyl chlorides, and iodonitrobenzoyl chlorides. As examplesof the aminonaphthalene/ sulphonic acids may be mentioned 1:8-aminonaphthol-3zfi disulphonic acid, l-haphthylamine-4 8 disulphonic acid, l-naphthylamine-4 (5 8-trisulphonic acid, l-naphthylamine-3 (S S-trisulphonic acid, chloi'onaphthylamine sulphonic acid, bro1noor iodonaphthylamine sulphonic acids (obtained by halogenating naphthylamine sulphonic acids by known methods or by halogenating acetylnaphthylamine sulphonic acids b known methods and hydrolyzing the pro ucts), alkoxynaphthylamine sulphonic acids, 1:5-amino-naphthol-Tsulphonic acid, and 2 8-a1uinonaphthol-8 S-disulphonic acid. As examples of the amino-acenaphthene sulphonic acids may be mentioned 4-amino acenaphthene-5-sulphonic acid as: t, ,1

' precipitation of the substance from the solution by acetone, ether or other suitable precipitant.

As an illustration of one method of carrying out our invention we describe below the process for preparing a compound having the probable structure:

OaNn

SOsNa I some T SO|Na NH-CO NH-C 0 NH Our invention is in no way limited to the substances mentioned in this example nor to the proportions there used, nor to the de tails of the method of preparation given. The parts are by weight.

Emcimple.

122 parts of l-naphtl1ylamine-4z6:8-trisulphonic acid are stirred into 600 parts of water and made just alkaline with caustic soda. 100 parts of sodium acetate and parts of o-nitro-p-toluyl chloride are added. After being stirred until free amino group can no longer be detected, the solution is filtered and reduced at the boil with 100 parts of iron, 150 parts of water and 20 parts of 10 per cent hydrochloric acid. The mixture is made alkaline with soda ash, filtered and cooled. 50 parts of m-nitrobenzoyl chloride are now added, and after stirring for 24 hours the whole is heated to C. and liltered. The product is salted out from the filtrate, washed with brine, pressed, re-dissolved in 900 parts of hot water, and reduced as before with iron, water and a little acid. Soda ash is added, iron sludge is removed by filtration, the filtrate is made neutral to litmus and evaporated underreduced pressure to half its volume. 110 parts of salt are added, and after filtering of]: impurities and making alkaline once more Wit-h soda ash, colourless crystals of sodium aminobenzoylamino toluylamino naphthalenetrisulphonate separate out on standing.

96 parts of this product are dissolved in 300 parts of water and made acid to Congo paper with dilute hydrochloric acid. Ice is added to reduce the temperature to 0 C. and the solution is diazotized with Lil) parts of 10 per cent hydrochloric acid and 8.8 parts of sodium nitrite in aqueous solution. The diazo compound is reduced with Si parts of sodium hydrosulphite dissolved in water. When reduction is complete, the solution is heated to boiling for a short time to hydrolyze the hydrazine-sulphonic acid, and the cooled solution is then carefully neutralized with alkali and evaporated to dryness (preferably under reduced pressure). The solid product is extracted with methyl alcohol and the filtrate poured into 56 times its bulk of absolute ethyl alcohol. The precipitate is the urified hydrazine derivative. 63 parts oi this product are dissolved in 200 parts of water with the addition of 30 parts of sodium carbonate. A solution of thiophosgene in toluene is added in portions with stirring until 30 parts of thiophosgene have been used up.

resents a sulphonated naphthalene residue containing more than one fused ring and de-.

rived from a hydrocarbon having a molecular weight of: more than 120 and less than 160, and Q and R represent divalent aromatic The aqueous layer is then separated, carefully neutralized with 10 per.

IUD

residues containine not more than two cyclic nuclei, the said thiocarlmzides bein; white or pale-colored powders, soluble in aqueous alkali, and hydrolyzed when boiled with caustic alkali forming an alkali metal thiocarbonate and a hydrazine,

PNHXQ-NIIY-R-NIINlI 2. As new materials thiocarlnizides having the formula r 1\'n-c0 im co n-Nm,

ts PNH-CO-Q-NHCO-RI-LIT2 in which P represents a sulphonated naphthalene residue containing more than one fused ring and derived from a hydrocarbon having a molecular weight of more than and less than 160, and Q, and R represent divalent aromatic residues containing not more than two cyclic nuclei, the said thiocarbazides having the formula and eventually the constituent amines P-NH: and I COOHQ-NH2,

and the hydrazine,

cooiI-R- N1I-Ni-I 3. As new materials thiocarbazides having the formula P--NHC0QNH--C0-R-N2H,

cs r NH co o-NneoR-i- 1 n in which P represents a sulphonated naphthalene residue contaming more than one fused ring and derived from a hydrocarbon having a molecular weight of more than 120 and less than 160, and Q and R are monocychc oramat-ic residues.

4. As new materials th ocarbazides having the formula PNHCO-QNH-CORN2H2 P-NHCOQ-NHCORN:H,

in which P represents a sulphonated naphthalene residue containing more than one fused ring and derived from a hydrocarbon having a molecular weight of more than 120 and less than 160, and Q is a tolylene residue and R is a monocyclic aromatic residue.

5. As new materials thiocarbazides having the formula fused ring and derived from a hydrocarbon havingva molecular weight of more than 120 and less than 160, Q is the 2:4-tolylne residue (CH 1) and R is a phenylene residue.

7. As new materials thiocarbazides having in which P represents a sulphonated naphin which P represents a trisulphonated naphthalene residue containing more. than one .fused ring and derived from a hydrocarbon having a molecular weight of more than 120 and less than 160, Q, is the 2:4-tolylene residue (CH =l) and R is a phenylene residue,

the final fission products being a naphthylamine-trisulphonic acid, 3-amino-t-methylbenzoic acid, and an aminophenylhydrazine.

9. As a new material the substance having the probable formula:

SOaNa- NH-CO Nn-oo NE} soma DOJNE l,

v s SOaNfl. v l

some -oH T some NH-CO NH-oo NH the said substance being a white powder, readily soluble in water and dissolving in 10 per cent aqueous caustic soda toa red solution whichbecomes gradually yellow when boiled, the-yellow solution showing the characteristic reducing power of a hydrazine to- I wards ainmoniacal copper sulphate and a1nmoniacal silver solutions.

In testimony whereof .we afiix our signatures. A

GEORGE MALCOLM DYSON. FREDERICK ALFRED MASON. ARNOLD RENSHAW, M. D. 

